Antiulcer compounds

ABSTRACT

An antiulcer composition comprising phytyl oleate or isophytyl oleate as the active ingredient is described.

This is a divisional application of U.S. Patent Application Ser. No.889,568 filed Mar. 23, 1978, now U.S. Pat. No. 4,221,810, granted Sept.9, 1980.

The present invention relates to an antiulcer agent comprising acompound represented by the general formula

    R--Z

wherein R means a saturated or unsaturated aliphatic group which maypossess a hydroxyl group or an epoxy ring as substituent, and Z meansCOOR' (wherein R' means hydrogen atom, or alkyl group, phytyl group,isophytyl group, dihydrophtyl group, decaprenyl group or solanesylgroup) or hydroxyl group, as its effective component.

A good number of compounds having antiulcer activity such as gefarnate(Cefanil, Trade name of Sumitomo Chemical Co. Ltd. for3,7-dimethyl-2,6-octadienyl-5,9,13-trimethyl-4,8,12-tetradecatrienoate)and the like have been proposed for the treatment of peptic ulcer.However, no compounds so far reported possess satisfactory preventiveand curative effects for peptic ulcer. As the results of extensivestudies in this field, we have found a group of compounds which are veryeffective for the therapy of peptic ulcer.

The compounds of this invention, represented by the general formula (I)may be prepared, for instance, according to the process described below.##STR1##

In the above formulae, R means a saturated or unsaturated aliphaticgroup, which may have a hydroxyl group or an epoxy ring as substituent,X means a halogen atom, R' means a lower alkyl group and R¹ means analkyl, phytyl, isophytyl, dihydrophytyl, decaprenyl or solanesyl groupor α-tocopherol residue. Decaprenyl group is 3, 7, 11, 15, 19, 23, 27,31, 33, 39-decamethyl-2,6,10,14,18,22,26,30,34,38-tetracontadecaenylgroup.

First, an aliphatic halide represented by the general formula (II) iscondensed with a di-lower alkyl malonate ester represented by thegeneral formula (III) in an alcohol in the presence of an alkali metalalcoholate to produce a di-lower alkyl aliphatic malonate ester havingthe general formula (IV). The alcohol which is used for this reactionmay include methanol, ethanol, isopropanol, t-butanol and the like, andthe alkali metal which is used may include sodium, potassium and thelike. The reaction temperature is in the range of 60°-100° C., withabout 80° C. being preferable. The reaction period is preferably in therange of 2-10 hours, but normally the reaction is almost complete inabout 5 hours.

Then the di-lower alkyl aliphatic malonate ester represented by thegeneral formula (IV) is hydrolysed with an alkali in an alcohol, andthen neutralized with an acid to produce an aliphatic malonic acidhaving the general formula (V). The alcohol which may be used in thereaction may include metanol, ethanol and isopropanol, and the alkaliwhich is used may include sodium hydroxide, potassium hydroxide and thelike. The reaction is suitably carried out at 75°-85° C. for 3-5 hours.The resulting aliphatic malonic acid of the general formula (V) is thenheated under reduced pressure to effect decarboxylation to yield anacetic acid derivative represented by the general formula (I'). Ofcourse, some of such acetic acid derivatives, e.g. oleic acid, stearicacid, etc., are readily available under the market.

To obtain ester derivatives of those compounds, the acetic acidderivative represented by the above general formula (I') is condensedwith an alcohol represented by the general formula (VI) to form an alkylester of the acetic acid derivative with the general formula (I). Theester formation may be effected by any of the known methods such as acidchloride method, acid anhydride method, direct esterification,substitution method, ester exchange reaction, diazoalkyl method and thelike. However, to avoid side reactions being involved, the reactionconditions should desirably be kept as mild as possible. For example,when acid chloride method is adopted, an acetic acid derivative of thegeneral formula (I') or a salt thereof is dissolved or dispersed in asolvent such as benzene, toluene and the like, and with cooling andstirring, an halogenating agent such as oxalyl chloride, thionylchloride or phosphorus pentachloride is slowly added thereto. Afteragitating the mixture at room temperature for further 1-6 hours,followed by heating, if required, an acid halide is produced. Then theresulting acid halide is reacted with an alcohol without any solvent orin the presence of an inert solvent such as benzene, toluene, xylene andthe like, and in the presence of a base to produce an ester. The basewhich may be used in the reaction may include a tertiary organic basesuch as pyridine, quinoline, triethylamine, N,N-dimethylaniline, alkalior alkaline earth metal carbonate such as sodium carbonate, potassiumcarbonate, sodium bicarbonate, calcium carbonate, or alkali or alkalineearth metal hydroxide such as sodium hydroxide, potassium hydroxide andthe like. However, a tertiary organic base such as pyridine and the likeis preferred. The reaction is normally effected at 0°-80° C. for 1-5hours. After completion of the reaction, the reaction mixture is pouredinto water and extracted in a usual manner with an organic solvent suchas ethyl ether. The extract is washed sequentially with water, dilutehydrochloric acid, aqueous sodium bicarbonate solution and saturatedaqueous sodium chloride solution, and dried. Removal of the solvent byevaporation under reduced pressure yields an alkyl ester of the presentinvention.

When the esterification is to be effected by substitution reaction, forexample, no alkali metal salt, a silver salt or a tertiary organic basesalt such as triethylamine salt of an acetic acid derivative (I') isreacted with an alkyl halide or a sulfate or sulfonate ester of analcohol to produce an alkyl ester in its highly purified state. As asolvent used in the reaction, a polar solvent such asN,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide,hexamethyl phosphoric triamide and the like are especially preferable.The reaction is suitably carried out at room temperature to 120° C. for2-24 hours. After completion of the reaction, the reaction mixture isprocessed in a similar manner, as described above for the esterificationby acid chloride method, to produce an alkyl ester of the presentinvention.

The acetic acid derivatives of the present invention obtained by theprocess described above may, if required, be subjected to furtherpurification by vacuum distillation or column chromatography and thelike.

The physiological activity of the active compounds according to thepresent invention will be shown below.

In the case of reserpine-induced ulcer, the assay was performedaccording to the description in "Arch. Int. Pharmacodym. Ther. 147,113(1964)", and in the case of acetic acid-induced ulcer, the assay wasperformed according to the method described in "Jap. J. Pharmac. 19,418(1969)", by inducing experimental ulcer in rat and evaluating the effectthereon of the compounds tested.

I. Reserpine-induced ulcer (Preventive test)

Groups of rats, each consisting of 6 male SD rats weighing 150-200 gwere used. After 24 hours'fasting, a sample compound was orallyadministered to the rat at the dose of 100 mg/kg body weight, and 30minutes after the administration, reserpine was intraperitoneallyinjected at the dose of 15 mg/kg body weight. Eighteen hours after theadministration, the rats were killed with chloroform. The stomach wastaken out, and severity of the hemorrhaging lesion was evaluatedaccording to the method as above ("Arch. Int. Pharmacodym. Ther. 147,113(1964)).

The preventive ratio was calculated using the following equation,##EQU1## wherein the control animals were intraperitoneally givenreserpine only, at the dose of 15 mg/kg body weight.

The results are given in Table 1, using the following signs.

    ______________________________________                                        Preventive Ratio Sign                                                         ______________________________________                                          -10%           ±                                                         10%-40%          +                                                            40%-60%          ++                                                           60%-             +++                                                          ______________________________________                                    

II. Acetic acid-induced ulcer (Curative test)

Groups of rats, each consisting of 6 male SD rats weighing 150-200 gwere used. The stomach of ether-anesthesized rat was exposed and whiletaking care not to injure blood vessels, 0.05 ml of 15% aqueous aceticacid solution was injected underneath the serosa. On the 14th day, therats were killed with chloroform, the stomach taken out and the area ofthe infected lesion measured.

The curative ratio was calculated using the above equation: ##EQU2##

The results are shown in Table 2, using the following signs:

    ______________________________________                                        Curative Ratio  Sign                                                          ______________________________________                                          -10%          ±                                                          10%-25%         +                                                             25%-40%         ++                                                            40%-            +++                                                           ______________________________________                                    

                  TABLE 1                                                         ______________________________________                                                           Preventive                                                 Compounds          effect     LD.sub.50 (g/kg)                                ______________________________________                                        Phytylacetic acid  +          >5                                              Methyl phytylacetate                                                                             +          >5                                              Decaprenylacetic acid                                                                            ++         >4                                              Isopropyl phytylacetate                                                                          +          >5                                              Phytyl acetate     ++         >5                                              Phytyl geranylacetate                                                                            +          >5                                              Phytyl citronellylacetate                                                                        +          >5                                              Phytyl farnesylacetate                                                                           +          >5                                              Phytyl laurate     ++         >5                                              phytyl palmitate   ++         >5                                              Phytyl oleate      +++        >4                                              Isophytyl oleate   +++        >4                                              Phytyl phytylacetate                                                                             ++         >5                                              Phytyl erucate     +          >4                                              Phytyl brassidate  +          >4                                              Phytyl decaprenylacetate                                                                         +          >4                                              Dihydrophytyl stearate                                                                           +          >4                                              Dihydrophytyl oleate                                                                             +          >4                                              Solanesyl acetate  ++         >4                                              Solanesyl farnesylacetate                                                                        +          >4                                              Solanesyl oleate   +          >4                                              Solanesyl phytylacetate                                                                          +          >4                                              Solanesyl solanesylacetate                                                                       +          >4                                              Solanesyl decaprenylacetate                                                                      +          >4                                              Decaprenyl acetate ++         >5                                              Decaprenyl elaidate                                                                              +          >5                                              Decaprenyl oleate  ++         >5                                              Decaprenyl phytylacetate                                                                         ++         >5                                              α-Tocopheryl geranylacetate                                                                ++         >4                                              α-Tocopheryl citronellylacetate                                                            +++        >4                                              α-Tocopheryl farnesylacetate                                                               ++         >4                                              α-Tocopheryl phytylacetate                                                                 +          >4                                              α-Tocopheryl solanesylacetate                                                              ++         >4                                              α-Tocopheryl decaprenylacetate                                                             +          >4                                              Solanesol          +          >4                                              Isodecaprenol      +          >4                                              Saturated decaprenol                                                                             +          >5                                              Gefarnate (control)                                                                              +                                                          ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                                           Curative                                                   Compounds          effect    LD.sub.50 (g/kg)                                 ______________________________________                                        Phytylacetic acid  +         >5                                               Solanesylacetic acid                                                                             +         >4                                               Methyl solanesylacetate                                                                          ++        >4                                               Ethyl solanesylacetate                                                                           + +       >4                                               Decaprenylacetic acid                                                                            +++       >4                                               Methyl decaprenylacetate                                                                         ++        >4                                               Ethyl decaprenylacetate                                                                          +++       >4                                               Isopropyl decaprenylacetate                                                                      +         >4                                               Isoamyl decaprenylacetate                                                                        +         >4                                               Phytyl acetate     +         >5                                               Phytyl stearate    +         >4                                               Phytyl oleate      +++       >4                                               Isophytyl oleate   +++       >4                                               Phytyl elaidate    +         >4                                               Phytyl linoleate   +         >4                                               Phytyl petroselinate                                                                             ++        >5                                               Phytyl ricinoleate +         >5                                               Phytyl 9,10-epoxystearate                                                                        +         >5                                               Phytyl brassidate  ++        >4                                               Phytyl decaprenylacetate                                                                         +         >4                                               Solanesyl geranylacetate                                                                         +         >4                                               Solanesyl oleate   ++        >4                                               Decaprenyl acetate +         >5                                               Decaprenyl geranylacetate                                                                        +         >5                                               Decaprenyl farnesylacetate                                                                       +         >5                                               Decaprenyl oleate  ++        >5                                               Decaprenyl petroselinate                                                                         ++        >4                                               Decaprenyl brassidate                                                                            ++        >4                                               Decaprenyl phytylacetate                                                                         ++        >5                                               Decaprenyl solanesylacetate                                                                      +         >5                                               Decaprenyl decaprenylacetate                                                                     +         >5                                               α-Tocopheryl geranylacetate                                                                +         >4                                               α-Tocopheryl farnesylacetate                                                               ++        >4                                               α-Tocopheryl phytylacetate                                                                 +++       >4                                               Solanesol          ++        >4                                               Decaprenol         +++       >4                                               Isodecaprenol      ++        >4                                               Saturated decaprenol                                                                             + +       >5                                               Gefarnate (Control)                                                                              ±                                                       ______________________________________                                    

The results given above clearly show that the active compounds accordingto the present invention possess excellent antiulcer activity. Moreover,the compounds of the present invention possess therapeutic effect notonly on reserpine- or acetic acid-induced ulcer but also on ulcers ofvarious other types. As shown in Tables 1 and 2, the acute toxicity ofthe present compounds is quite low, when examined by intraperitonealroute in mice. The active compounds of the present invention may beadministered intravenously, subcutaneously, intramuscularly or orally.Oral and intramuscular administration is preferred. The dosage of thepresent active compounds used for the treatment of a human adult is inthe range of 100-1000 mg per day, with the range of 200-300 mg per daybeing preferable.

For oral administration, the present active compounds may take the formof tablet, granules or powder; if required the granules or powder may beformulated as capsules and used in the form of dosage unit. Those solidpreparations for oral administration may contain any ordinary excipientsuch as anhydrous silicic acid, magnesium metasilicate aluminate,synthetic aluminum silicate, lactose, sucrose, corn starch,microcrystalline cellulose, hydroxypropyl starch or glycine, bindingagent such as gum arabic, gelatin, tragacanth, hydroxypropyl celluloseor polyvinyl pyrrolidone, lubricant such as magnesium stearate, talc orsilica, disintegrating agent such as potato starch orcarboxymethylcellulose calcium salt, or wetting agent such aspolyethyleneglycol, sorbitan monooleate, polyoxyethylene-hardened castoroil, sodium laurylsulfate. The tablets may be coated in a usual manner.

Liquid preparations for oral administration may take the form of aqueousor oil emulsion or syrup, or dry powder preparation which may beredissolved in a suitable vehicle before use. Those liquid preparationsmay contain usual additives such as emulsifying aid, e.g. sugar syrup,methylcellulose, gelatin, hydroxyethylcellulose, emulsifying agent e.g.lecithin, sorbitan monooleate, polyoxyethylene-hardened castor oil,non-aqueous vehicle e.g. fractionated coconut oil, almond oil, arachisoil, or antiseptic agent e.g. methyl p-hydroxybenzoate, propylp-hydroxybenzoate or sorbic acid. Those preparations for oraladministration may, if required, contain preservatives, stabilizingagents and the like.

When the compounds are to be administered by injection, theirpreparations may take the form of oil solution, emulsion, aqueoussolution and the like. Those solvent may contain usual emulsifyingagent, stabilizing agent and the like.

Those pharmaceutical compositions may contain more than 1%, preferably5-50%, of the present compounds, depending on the route ofadministration.

The followings are the examples of the synthesis of the compounds and oftheir pharmaceutical preparations, but they are not intended to limitthe scope of the present invention.

EXAMPLE 1 Decaprenylacetic Acid ##STR2##

Sodium metal (3.0 g) was dissolved in 200 ml of absolute ethanol and25.0 g of diethyl malonate was added thereto. Then, under reflux, at75°-82° C., 100 g of decaprenyl bromide was added dropwise over 4 hours.After further stirring at 75°-82° C. for one hour, the reaction mixturewas poured into water and extracted with ethyl acetate. The ethylacetate extract was sequentially washed with water and saturated sodiumchloride solution, and then dried over anhydrous magnesium sulfate.After evaporating off the ethyl acetate under reduced pressure theresultant oily residue weighing 111.2 g was, with the addition of 26.1 gof potassium hydroxide in 500 ml of ethanol, heated at 78°-80° C. for3.0 hours in nitrogen atmosphere. After cooling, the reaction mixturewas acidified to pH 3.0 with concentrated hydrochloric acid andextracted with ether. The ether extract was sequentially washed withwater and saturated sodium chloride solution, and dried over magnesiumsulfate. The ether was evaporated off under reduced pressure and theresulting concentrate (89.0 g) was heated at 150° C. under reducedpressure (1-10 mm Hg) for 3 hours to complete decarboxylation.Purification through silica gel column chromatography gave 27.4 g ofsemicrystalline decaprenylacetic acid.

    ______________________________________                                        1R ν.sub.max cm.sup.-1 :                                                                 2800-2400 (COCH), 1710 (CO),                                                  1665 (CC), 840                                                  NMR δ .sub.TMS.sup.CDCl.sbsp.3:                                                        ##STR3##                                                                      ##STR4##                                                                     11.15 (1H, CO.sub.2 H)                                          ______________________________________                                    

Elementary analysis: Calculated for C₅₂ H₈₄ O₂ : C, 84.26; H, 11.42(%).Found: C, 84.47; H, 11.27(%).

Solanesylacetic acid was prepared in a similar manner as that describedin Example 1. The physical constants are given below.

    ______________________________________                                        Solanesylacetic acid                                                           ##STR5##                                                                     ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                                 2800-2400 (COCH), 1710 (CO),                                                  1665 (CC), 840                                                     NMR δ .sub.TMS.sup.CDCl.sbsp.3:                                                     ##STR6##                                                                      ##STR7##                                                                     11.33 (1H, CO.sub.2 H)                                          ______________________________________                                    

Elementary analysis: Calculated for C₄₇ H₇₆ O₂ : C, 83.87; H, 11.38(%).Found: C, 84.25; H, 11.18(%).

EXAMPLE 2 Ethyl Decaprenylacetate

Sodium metal (0.46 g) was dissolved in 200 ml of absolute ethanol, and122 g of decaprenylacetic acid was added thereto. After stirring forsome time, the ethanol was evaporated under reduced pressure. To adispersion of the residue in 160 ml of dry benzene 10 ml ofoxalylchloride was added over about 15 minutes, under ice cooling andwith stirring, and the mixture was further stirred for two hours at roomtemperature. After concentration of the reaction mixture under reducedpressure, 200 ml of dry ethylene chloride was added thereto. The solublefraction was added dropwise over about 15 minutes to an ice-cooled andstirred solution of 5 ml of ethanol in 100 ml of dry ethylene chlorideand 6 ml of pyridine. The resulting solution was further stirred for 2hours at room temperature. The reaction mixture was poured into 200 mlof stirred ice water and extracted with ether. The ether extract wassequentially washed with water, dilute hydrochloric acid, saturatedsodium bicarbonate solution and saturated sodium chloride solution andthen the solvent was evaporated under reduced pressure. The residue waspurified by means of silica gel column chromatography to give 8.7 g ofethyl decaprenylacetate as colourless oil.

    ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                                 1740 (CO), 1670 (CC)                                              NMR δ .sub.TMS.sup.CDCl.sbsp.3:                                                      ##STR8##                                                                      ##STR9##                                                                     (CH.sub.2 CO), 4.03 (2H, CH.sub.2 O), 5.05                                     ##STR10##                                                      ______________________________________                                    

Elementary analysis: calculated for C₅₄ H₈₈ O₂ : C, 84.31; H, 11.53(%).Found: C, 84.60; H, 11.34(%).

The following compounds were prepared in an analogous manner. Theresults of elementary analysis and nuclear magnetic resonance spectrummeasurements of those compounds are shown in Tables 3 and 4respectively.

                  TABLE 3                                                         ______________________________________                                        Com-                Em-      Elementary analysis (%)                          pound               pirical  Calculated                                                                            Found                                    No.   Compounds     formula  C    H    C    H                                 ______________________________________                                        1     Methyl        C.sub.48 H.sub.78 O.sub.2                                                              83.90                                                                              11.44                                                                              84.02                                                                              11.49                                   solanesylacetate                                                        2     Ethyl         C.sub.49 H.sub.80 O.sub.2                                                              83.94                                                                              11.50                                                                              83.88                                                                              11.63                                   solanesylacetate                                                        3     Methyl        C.sub.53 H.sub.86 O.sub.2                                                              84.29                                                                              11.48                                                                              84.46                                                                              11.57                                   decaprenylacetate                                                       4     Isopropyl     C.sub.55 H.sub.90 O.sub.2                                                              84.33                                                                              11.58                                                                              84.35                                                                              11.51                                   decaprenylacetate                                                       5     Isoamyl       C.sub.57 H.sub.94 O.sub.2                                                              84.27                                                                              11.79                                                                              83.91                                                                              11.50                                   decaprenylacetate                                                       6     Methyl        C.sub.23 H.sub.44 O.sub.2                                                              78.34                                                                              12.58                                                                              78.41                                                                              12.62                                   phytylacetate                                                           7     Isopropyl     C.sub.25 H.sub.48 O.sub.2                                                              78.88                                                                              12.71                                                                              78.82                                                                              12.63                                   phytylacetate                                                           ______________________________________                                    

                                      TABLE 4                                     __________________________________________________________________________    δ values (CDCl.sub.3 solution, TMS, 60 MHz)                              No.Compounds                                                                        ##STR11##                                                                          ##STR12##                                                                        ##STR13##                                                                           CH.sub.2 CO                                                                        CH.sub.2 O                                                                         ##STR14##                                                                          Remarks                                   __________________________________________________________________________    1     --   1.60                                                                             2.00  2.30 --   5.10(9H)                                                                           3.65(3H, CH.sub.3 OCO)                       2   --   "  "     "    4.10(2H)                                                                           5.10(9H)                                                                            ##STR15##                                   3   --   "  "     "    --   5.05(10H)                                                                          3.60(3H, CH.sub.3 OCO)                       4   1.2  "  "     "    --   5.10(10H)                                                                           ##STR16##                                    5  0.93 "  "     "    4.05(2H)                                                                           5.07(10H)                                                                            --                                       6     0.87 "  "     "    --   5.05(1H)                                                                           3.63(3H, CH.sub.3 OCO)                       7   0.87, 1.22                                                                         "  1.95  "    --   5.05(1H)                                                                            ##STR17##                                 __________________________________________________________________________     The numbers in the column under "Compounds" correspond to the respective      compound numbers in Table 3.                                             

EXAMPLE 3 Phytyl Oleate and Isophytyl Oleate ##STR18##

A mixture of 15 g of phytol, 11 g of dicyclohexylcarbodiimide and 0.1 gof cuprous chloride was stirred at 90°-100° C. for two hours undernitrogen, to which 16 g of oleic acid was added, followed by further twohours' stirring at 90°-100° C. After cooling, the reaction mixture wasadded with 100 ml of n-hexane, freed from any insoluble matters throughfiltration and the filtrate was concentrated under reduced pressure. Theresidue was subjected to silica gel chromatography to yield 12.6 g ofisophytyl oleate from the first eluting fraction and 5.9 g of phytyloleate from the later eluting fraction. Physical constants for phytyloleate are as follows.

    ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                               1730 (CO), 1670 (CC), 970                                         NMR δ .sub.TMS.sup.CDCl.sbsp.3:                                                      ##STR19##                                                                     ##STR20##                                                                     ##STR21##                                                        ______________________________________                                    

Elementary analysis: Calculated for C₃₈ H₇₂ O₂ : C, 81.36; H, 12.94(%).Found: C, 81.49; H, 13.08(%).

Physical constants for isophytyl oleate are as follows.

    ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                               3100 (CH.sub.2), 1730 (CO), 1640                                              (CC), 995, 925                                                      NMR δ .sub.TMS.sup.CCl.sbsp.4:                                                     ##STR22##                                                                     ##STR23##                                                                     ##STR24##                                                                    (1H, CH)                                                          ______________________________________                                    

Elementary analysis: Calculated for C₃₈ H₇₂ O₂ : C, 81.36; H, 12.94(%).Found: C, 81.51; H, 12.87(%).

EXAMPLE 4 Phytyl Decaprenylacetate ##STR25##

Sodium metal (0.23 g) was dissolved in 100 ml of absolute ethanol.Decaprenylacetic acid (6.1 g) was added to the solution and, afterstirring for some time, the ethanol was evaporated under reducedpressure. To a dispersion of the resulting residue in 80 ml of drybenzene, 5 ml of oxalyl chloride was added over about 15 minutes underice cooling and with stirring. The mixture was further stirredovernight. The reaction mixture was concentrated under reduced pressureand was added with 100 ml of dry ethylene chloride. The soluble fractionwas added dropwise over about 15 minutes to an ice-cooled and stirredsolution of 2.9 g of phytol in 50 ml of dry ethylene chloride and 3 mlof pyridine, and the mixture was further stirred for 3 hours at roomtemperature. The reaction mixture was poured into 100 ml of stirred icewater and extracted with ether. The ether extract was sequentiallywashed with water, 5% hydrochloric acid, saturated sodium bicarbonatesolution and saturated sodium chloride solution, and then ether wasevaporated off under reduced pressure. The residue was purified bysilica gel column chromatography to give 5.2 g of phytyldecaprenylacetate as colourless oil.

    ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                              1740 (CO), 1660 (CC)                                               NMR δ .sub.TMS.sup.CDCl.sbsp.3:                                                     ##STR26##                                                                     ##STR27##                                                                     ##STR28##                                                         ______________________________________                                    

Elementary analysis: Calculated for C₇₂ H₁₂₂ O₂ : C, 84.80; H, 12,06(%).Found: C, 84.96; H, 12.21(%).

The following compounds were prepared in an analogous manner. Theresults of infrared absorption (IR) and elementary analysis of thosecompounds are shown in Table 5, and that of nuclear magnetic resonance(NMR) spectrum measurements in Table 6.

                                      TABLE 5                                     __________________________________________________________________________                                 Elementary analysis (%)                          Compound           IR (cm.sup.-1)                                                                          Calculated                                                                          Found                                      No.   Compounds    ν C═O                                                                       ν C═C                                                                       C  H  C  H  C,H,O                                __________________________________________________________________________    8     Phytyl geranylacetate                                                                      1730 1670 80.93                                                                            12.31                                                                            80.94                                                                            12.16                                                                            C.sub.32 H.sub.58 O.sub.2            9     Phytyl citronellylacetate                                                                  "    "    80.61                                                                            12.68                                                                            80.88                                                                            12.29                                                                            C.sub.32 H.sub.60 O.sub.2            10    Phytyl farnesylacetate                                                                     "    "    80.85                                                                            12.25                                                                            80.96                                                                            12.76                                                                            C.sub.37 H.sub.66 O.sub.2            11    Phytyl phytylacetate                                                                       "    "    81.75                                                                            13.07                                                                            82.12                                                                            13.24                                                                            C.sub.42 H.sub.80 O.sub.2            12    Phytyl laurate                                                                             "    "    80.26                                                                            13.05                                                                            80.23                                                                            13.11                                                                            C.sub.32 H.sub.62 O.sub.2            13    Phytyl palmitate                                                                           "    "    80.83                                                                            13.19                                                                            80.74                                                                            13.06                                                                            C.sub.36 H.sub.70 O.sub.2            14    Phytyl stearate                                                                            "    "    81.07                                                                            13.25                                                                            81.38                                                                            13.02                                                                            C.sub.38 H.sub.79 O.sub.2            15    Phytyl elaidate                                                                            "    "    81.36                                                                            12.94                                                                            81.42                                                                            13.15                                                                            C.sub.38 H.sub.72 O.sub.2            16    Phytyl linoleate                                                                           "    "    81.65                                                                            12.62                                                                            81.63                                                                            12.47                                                                            C.sub.38 H.sub.77 O.sub.2            17    Phytyl petroselinate                                                                       "    "    81.36                                                                            12.94                                                                            81.41                                                                            12.91                                                                            C.sub.38 H.sub.72 O.sub.2            18    Phytyl ricinoleate                                                                         "    "    79.10                                                                            12.58                                                                            78.70                                                                            12.23                                                                            C.sub.38 H.sub.72 O.sub.3            19    Phytyl 9,10-epoxystearate                                                                  "    "    79.10                                                                            12.58                                                                            79.19                                                                            12.64                                                                            C.sub.38 H.sub.72 O.sub.3            20    Phytyl erucate                                                                             "    "    81.75                                                                            13.07                                                                            81.69                                                                            12.91                                                                            C.sub.42 H.sub.80 O.sub.2            21    Phytyl brassidate                                                                          "    "    81.75                                                                            13.07                                                                            81.84                                                                            12.95                                                                            C.sub.42 H.sub.80 O.sub.2            22    Dihydrophytyl stearate                                                                     1740 --   80.78                                                                            13.56                                                                            80.91                                                                            13.58                                                                            C.sub.38 H.sub.76 O.sub.2            23    Dihydrophytyl oleate                                                                       "    "    81.07                                                                            13.25                                                                            81.22                                                                            13.36                                                                            C.sub.38 H.sub.74 O.sub.2            __________________________________________________________________________

                                      TABLE 6                                     __________________________________________________________________________    δ values (CDCl.sub.3 solution, TMS, 60 MHz)                              No.Compound                                                                         ##STR29##                                                                        ##STR30##                                                                           ##STR31##                                                                          ##STR32##                                                                           CH.sub.2 CO                                                                        CH.sub.2 O                                                                         ##STR33##                                                                          Remarks                             __________________________________________________________________________     8    0.85                                                                             1.20  1.60, 1.68                                                                         1.95  2.20 4.44 (2H)                                                                          5.10 (3H)                                  9    "  "     1.60, 1.70                                                                         1.90  "    4.45 (2H)                                                                          5.10 (2H)                                 10    "  1.30  1.60, 1.70                                                                         1.95  "    4.50 (2H)                                                                          5.10 (4H)                                 11    "  "     1.67 1.90  "    4.50 (2H)                                                                          5.10 (2H)                                 12    "  1.25  1.70 1.95  "    4.57 (2H)                                                                          5.30 (1H)                                 13    "  "     "    "     2.20 4.53 (2H)                                                                          5.20 (1H)                                 14    "  1.30  "    "     "    4.57 (2H)                                                                          5.30 (1H)                                 15    0.87                                                                             1.23  1.67 "     "    4.45 (2H)                                                                          5.27 (3H)                                   16  0.85                                                                             1.25  1.68 "     "    4.55 (2H)                                                                          5.35 (5H)                                                                           ##STR34##                             17  "  "     1.65 "     2.30 4.53 (2H)                                                                          5.20 (3H)                                   18  "  1.30  "    "     2.20 4.55 (2H)                                                                          5.30 (3H)                                                                           ##STR35##                              19 "  "     1.70 "     2.30 4.60 (2H)                                                                          5.32 (1H)                                                                           ##STR36##                             20  "  1.30  1.70 2.0   2.30 4.55 (2H)                                                                          5.27 (3H)                                 21    "  1.25  1.68 1.95  "    4.55 (2H)                                                                          5.30 (3H)                                 22    "  "     --   --    2.27 4.10 (2H)                                                                          --                                        23    "  1.27  --   2.0   2.30 4.10 (2H)                                                                          5.32 (2H)                                 __________________________________________________________________________

EXAMPLE 5 Solanesyl Oleate ##STR37##

Sodium oleate (6.4 g) was dispersed in 60 ml of dry benzene containing 1ml of dry pyridine, and 7 ml of oxalyl chloride was added thereto withstirring and under ice-cooling. The mixture was stirred further for 2hours at room temperature. After concentration under reduced pressure,the reaction mixture was stirred with 80 ml of dry benzene, and then thesoluble fraction was added over about 20 minutes to a solution of 15 gof solanesol in 100 ml of dry benzene and 8 ml of dry pyridine under icecooling and with stirring. The mixture was further stirred for 2 hoursat room temperature. The reaction product was poured into 150 ml ofstirred ice water, extracted with ether, and the ether extract wassequentially washed with water, dilute hydrochloric acid, saturatedsodium bicarbonate solution and saturated sodium chloride solution. Theremoval of the solvent under reduced pressure and silica gel columnchromatography of the residue gave 14.4 g of solanesyl oleate ascolourless oil.

    ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                                 1730 (CO), 1670 (CC)                                            NMR δ .sub.THS.sup.CDCl.sbsp.3:                                                        ##STR38##                                                                     ##STR39##                                                                    (CH.sub.2 CO), 4.58 (2H, CH.sub.2 O), 5.0                                      ##STR40##                                                      ______________________________________                                    

Elementary analysis: Calculated for C₆₃ H₁₀₆ O₂ : C, 84.50; H, 11.93(%).Found: C, 84.71; H, 11.95(%).

The following compounds were prepared in an analogous manner. Theresults of elementary analysis and nuclear magnetic resonance spectrum(NMR) measurements of those compounds are summarized in Table 7 andTable 8 respectively.

                  TABLE 7                                                         ______________________________________                                        Com-                     Elementary analysis (%)                              pound              Empirical Calculated                                                                            Found                                    No.   Compounds    formula   C    H    C    H                                 ______________________________________                                        24    Solanesyl    C.sub.57 H.sub.92 O.sub.2                                                               84.59                                                                              11.46                                                                              84.60                                                                              11.25                                   geranylacetate                                                          25    Solanesyl    C.sub.62 H.sub.100 O.sub.2                                                              84.87                                                                              11.48                                                                              84.66                                                                              11.38                                   farnesylacetate                                                         26    Solanesyl    C.sub.67 H.sub.114 O.sub.2                                                              84.47                                                                              12.06                                                                              84.75                                                                              11.77                                   Phytylacetate                                                           27    Solanesyl    C.sub.92 H.sub.148 O.sub.2                                                              85.91                                                                              11.60                                                                              86.32                                                                              11.48                                   solanesylacetate                                                        28    Solanesyl    C.sub.97 H.sub.156 O.sub.2                                                              86.03                                                                              11.61                                                                              86.34                                                                              11.37                                   decaprenylacetate                                                       29    Decaprenyl   C.sub.68 H.sub.114 O.sub.2                                                              84.75                                                                              11.92                                                                              84.91                                                                              11.99                                   elaidate                                                                30    Decaprenyl   C.sub.68 H.sub.114 O.sub.2                                                              84.75                                                                              11.92                                                                              85.02                                                                              12.14                                   oleate                                                                  31    Decaprenyl   C.sub.68 H.sub.114 O.sub.2                                                              84.75                                                                              11.92                                                                              84.60                                                                              11.78                                   petroselinate                                                           32    Decaprenyl   C.sub.72 H.sub.122 O.sub.2                                                              84.80                                                                              12.06                                                                              84.95                                                                              12.33                                   brassidate                                                              33    Decaprenyl   C.sub.62 H.sub.100 O.sub.2                                                              84.87                                                                              11.48                                                                              85.07                                                                              11.18                                   geranylacetate                                                          34    Decaprenyl   C.sub.67 H.sub.108 O.sub.2                                                              85.10                                                                              11.51                                                                              85.42                                                                              11.54                                   farnesylacetate                                                         35    Decaprenyl   C.sub.72 H.sub.122 O.sub.2                                                              84.80                                                                              12.06                                                                              84.97                                                                              11.86                                   phytylacetate                                                           36    Decaprenyl   C.sub.97 H.sub.156 O.sub.2                                                              86.03                                                                              11.61                                                                              86.02                                                                              11.47                                   solanesylacetate                                                        37    Decaprenyl   C.sub.102 H.sub.164 O.sub.2                                                             86.11                                                                              11.62                                                                              86.47                                                                              11.75                                   decaprenylacetate                                                       ______________________________________                                    

                                      TABLE 8                                     __________________________________________________________________________    δ values (CDCl.sub.3 solution, TMS, 60 MHz)                              No.Compound                                                                         ##STR41##                                                                        ##STR42##                                                                           ##STR43##                                                                        ##STR44##                                                                           CH.sub.2 CO                                                                        CH.sub.2 O                                                                         ##STR45##                                  __________________________________________________________________________    24    -- --    1.60                                                                             1.97  2.30 4.50 (2H)                                                                          5.05 (11H)                                  25    -- --    1.60                                                                             1.98  2.30 4.45 (2H)                                                                          5.07 (12H)                                  26    0.85                                                                             1.23  1.60                                                                             2.00  2.20 4.45 (2H)                                                                          5.05 (10H)                                  27    -- --    1.60                                                                             1.97  2.30 4.50 (2H)                                                                          5.05 (18H)                                  28    -- --    1.60                                                                             1.98  2.30 4.45 (2H)                                                                          5.05 (19H)                                  29    0.85                                                                             1.25  1.58                                                                             1.97  2.25 4.45 (2H)                                                                          5.03 (12H)                                  30    0.85                                                                             1.30  1.65                                                                             2.05  2.20 4.60 (2H)                                                                          5.14 (12H)                                  31    0.87                                                                             1.30  1.60                                                                             2.00  2.30 4.55 (2H)                                                                          5.05 (12H)                                  32    0.85                                                                             1.30  1.60                                                                             1.95  2.20 4.50 (2H)                                                                          5.10 (12H)                                  33    -- --    1.60                                                                             2.00  2.30 4.45 (2H)                                                                          5.05 (12H)                                  34    -- --    1.58                                                                             1.97  2.30 4.45 (2H)                                                                          5.05 (13H)                                  35    0.85                                                                             1.20  1.60                                                                             1.98  2.20 4.45 (2H)                                                                          5.05 (11H)                                  36    -- --    1.60                                                                             1.97  2.30 4.50 (2H)                                                                          5.05 (19H)                                  37    -- --    1.60                                                                             1.98  2.30 4.45 (2H)                                                                          5.05 (20H)                                  __________________________________________________________________________

EXAMPLE 6 α-Tocopheryl Solanesylacetate ##STR46##

Solanesylacetic acid (7.4 g) was added to a solution of 0.26 g of sodiummetal dissolved in 100 ml of absolute ethanol, and after stirring forsome time, the ethanol was evaporated off under reduced pressure. Theresidue was dispersed in 100 ml of dry benzene. To the dispersion whichhad been added with 2-3 drops of dry pyridine, 5 ml of oxalyl chloridewas added under ice-cooling and with stirring. The mixture was furtheragitated for 2 hours at room temperature. After concentration of thereaction mixture at reduced pressure, 100 ml of dry ethylene chloridewas added thereto. The soluble fraction was added over about 15 minutesto a solution of 10.4 g of α-tocopherol dissolved in 100 ml of dryethylene chloride and 7 ml of dry pyridine, under ice cooling and withstirring. The mixture was further stirred for 2 hours at roomtemperature. The reaction mixture was poured into 100 ml of stirred icewater and extracted with ether. The ether extract was sequentiallywashed with water, 5% hydrochloric acid, saturated sodium bicarbonatesolution and saturated sodium chloride solution. The removal of thesolvent under reduced pressure and silica gel column chromatography ofthe resulting residue gave 4.8 g of α-tocopheryl solanesylacetate ascolourless oil.

    ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                              1760 (CO), 1670 (CC)                                               NMR δ .sub.TMS.sup.CDCl.sbsp.3:                                                     ##STR47##                                                                     ##STR48##                                                                     ##STR49##                                                                     ##STR50##                                                         ______________________________________                                    

Elementary analysis: Calculated for C₇₆ H₁₂₄ O₃ : C, 84.07; H, 11.51(%).Found: C, 84.28; H, 11.29(%).

The following compounds were prepared in an analogous manner. Theresults of elementary analysis and nuclear magnetic resonance spectrummeasurements of those compounds are summarized in Table 9 and Table 10respectively.

                  TABLE 9                                                         ______________________________________                                        Com-                     Elementary analysis (%)                              pound              Empirical Calculated                                                                            Found                                    No.   Compounds    formula   C    H    C    H                                 ______________________________________                                        38    α-Tocopheryl                                                                         C.sub.41 H.sub.68 O.sub.3                                                               80.86                                                                              11.26                                                                              81.17                                                                              11.05                                   geranylacetate                                                          39    α-Tocopheryl                                                                         C.sub.41 H.sub.70 O.sub.3                                                               80.59                                                                              11.55                                                                              80.88                                                                              11.39                                   citronellylacetate                                                      40    α-Tocopheryl                                                                         C.sub.46 H.sub.76 O.sub.3                                                               81.60                                                                              11.31                                                                              81.53                                                                              11.14                                   farnesylacetate                                                         41    α-Tocopheryl                                                                         C.sub.51 H.sub.90 O.sub.3                                                               81.54                                                                              12.08                                                                              81.80                                                                              11.89                                   phytylacetate                                                           42    α-Tocopheryl                                                                         C.sub.81 H.sub.130 O.sub.3                                                              84.46                                                                              11.38                                                                              84.39                                                                              11.35                                   decaprenylacetate                                                       ______________________________________                                    

                                      TABLE 10                                    __________________________________________________________________________    δ values (CDCl.sub.3 solution, TMS, 60 MHz)                              No.Compound                                                                         ##STR51##                                                                        ##STR52##                                                                           ##STR53##                                                                          ##STR54##                                                                           ##STR55##                                                                             ##STR56##                                                                                   ##STR57##                    __________________________________________________________________________    38    0.88                                                                             1.23  1.60, 1.67                                                                         1.90, 1.93                                                                          2.05    2.50          5.10 (2H)                     39    "  1.25  "    1.90, 1.95                                                                          "       "             5.05 (1H)                     40    "  "     "    "     "       "             5.10 (3H)                     41    "  "     1.68 "     2.07    "             5.15 (1H)                     42    "  "     1.60 1.97  2.05    "             5.05 (10H)                    __________________________________________________________________________

EXAMPLE 7 Saturated Decaprenol

Decaprenol (26 g) was dissolved in 300 ml of ethanol. A suspension of1.5 g of Raney-Ni (W-1) in 10 ml of ethanol was added thereto, andhydrogenation was performed in an autoclave at 80° C. for 10 hours withshaking under 90 kg/cm² of hydrogen. The catalyst was filtered off andthe filtrate was concentrated. The residue weighing 26 g was purified bymeans of silica gel column chromatography to give 7.2 g of saturateddecaprenol, the physical constants of which are given below.

    ______________________________________                                        IR ν.sub.max cm.sup.-1 :                                                                     3350 (--OH)                                                 NMR δ .sub.TMS.sup.CDCl.sbsp.3:                                                           3.70 (CH.sub.2 O), 1.20 (CH.sub.2)                                            0.85 (CH.sub.3)                                             ______________________________________                                    

Elementary analysis: Calculated for C₅₀ H₁₀₂ O: H, 14.29; C, 83.48(%).Found: H, 14.23; C, 83.38(%).

EXAMPLE 8 Preparation of Dihydrophytol

Phytol (30.0 g, 0.101 mol) was dissolved in 200 ml of ethanol. Asuspension of 1.8 g of Raney-Ni (W-1) in 5 ml of ethanol was addedthereto, and hydrogenation was carried out under hydrogen for about 5hours so that 2405 ml of hydrogen (theoretical volume at 24° C.; 2465ml) was absorbed. After filtering off the catalyst through a filterpaper, the ethanol was evaporated. Yield 29.9 g. Silica gel columnchromatography with benzene-hexane (1:1) gave 24.7 g of the titlecompound (yield 82.3%).

PREPARATION 1 Hard Capsules

Solanesylacetic acid (25 g) and 7.5 g of polyoxyethylene-castor oil weredissolved in acetone and then 25 g of anhydrous silicic acid was added.After evaporating the acetone off, the resulting product was mixed with5 g of carboxymethylcellulose calcium, 5 g of corn starch, 7.5 g ofhydroxypropylcellulose and 20 g of microcrystalline cellulose("Avicel"), and the whole was kneaded with the addition of 30 ml ofwater. The product was made into granules through a pelletizer equippedwith a No. 24 mesh screen (B.S.) ("Xtruder Twin"® of Fuji-Paudal Co.).The granules were dried to reduce the water content thereof to less than5%, and then sieved through a No. 16 mesh screen (B.S.). The granuleswere then filled into capsules using a filling machine, at the rate of190 mg per capsule.

PREPARATION 2 Soft Capsules

Methyl decaprenylacetate (50 g) and 130 g of fractionated coconut oilwere mixed together to form a homogeneous solution. A gelatin solutionconsisting of 93 g of gelatin, 19 g of glycerol, 10 g of D-sorbitol, 0.4g of ethyl p-hydroxybenzoate, 0.2 g of propyl p-hydroxybenzoate and 0.4g of titanium dioxide was prepared. Using manual punching method, softcapsules each containing 180 mg were prepared from a sheet of saidgelatin solution.

PREPARATION 3 Solution for Injection

Isopropyl decaprenylacetate (5 g), a proper quantity of arachis oil and1 g of benzyl alcohol were mixed together and the whole quantity wasmade to 100 ml with the addition of additional arachis oil. Onemilliliter each of the solution was aseptically filled in an ampoule andthe ampoule was heat sealed.

PREPARATION 4 Hard Capsules

Phytyl geranylacetate (25 g) and 7.5 g of polyoxyethylene-castor oilwere dissolved in acetone and then 25 g of anhydrous silicic acid wasadded. After evaporating the acetone off, the resulting product wasmixed with 5 g of carboxymethylcellulose calcium, 5 g of corn starch,7.5 g of hydroxypropylcellulose and 20 g of microcrystalline cellulose,and the whole was kneaded with the addition of 30 ml of water. Theproduct was made into granules through a pelletizer equipped with a No.24 mesh screen (B.S.) ("Xtruder Twin"® of Fuji-Paudal Co.). The granuleswere dried to reduce the water content thereof to less than 5% and thensieved through a No. 16 mesh screen (B.S.). The granules were thenfilled into capsules using a filling machine at the rate of 190 mg percapsule.

PREPARATION 5 Hard Capsules

Solanesyl oleate (25 g) and 7.5 g of polyoxyethylene-castor oil weredissolved in acetone and then 25 g of anhydrous silicic acid was added.After evaporating the acetone off, the resulting product was mixed with5 g of carboxymethylcellulose calcium, 5 g of corn starch, 7.5 g ofhydroxypropylcellulose and 20 g of microcrystalline cellulose, and thewhole was kneaded with the addition of 30 ml of water. The product wasmade into granules through a pelletizer equipped with a No. 24 meshscreen (B.S.) ("Xtruder Twin"® of Fuji-Paudal Co.). The granules weredried to reduce the water content thereof to less than 5% and thensieved through a No. 16 mesh screen (B.S.). The granules were thenfilled into capsules using a filling machine at the rate of 190 mg percapsule.

PREPARATION 6 Soft Capsules

Phytyl decaprenylacetate (50 g) and 130 g of fractionated coconut oilwere mixed together to form a homogeneous solution. A gelatin solutionconsisting of 93 g of gelatin, 19 g of glycerol, 10 g of D-sorbitol, 0.4g of ethyl p-hydroxybenzoate, 0.2 g of propyl p-hydroxybenzoate and 0.4g of titanium dioxide was prepared. Using this gelatin solution inmanual punching method, soft capsules each containing 180 mg wereprepared.

PREPARATION 7 Soft Capsules

Decaprenyl phytylacetate (50 g) and 130 g of fractionated coconut oilwere mixed together to form a homogeneous solution. A gelatin solutionconsisting of 93 g of gelatin, 19 g of glycerol, 10 g of D-sorbitol, 0.4of ethyl p-hydroxybenzoate, 0.2 g of propyl p-hydroxybenzoate and 0.4 gof titanium dioxide was prepared. Using this gelatin solution in manualpunching method, soft capsules each containing 180 mg were prepared.

PREPARATION 8 Solution for Injection

Phytyl oleate (5 g), a proper quantity of arachis oil and 1 g of benzylalcohol were mixed together and the whole quantity was made to 100 mlwith the addition of additional arachis oil. One milliliter each of thesolution was aseptically filled in an ampoule and the ampoules were heatsealed.

PREPARATION 9 Solution for Injection

Decaprenyl oleate (5 g), a proper quantity of arachis oil and 1 g ofbenzyl alcohol were mixed together and the whole quantity was made to100 ml with the addition of additional arachis oil. One milliliter eachof the solution was aseptically filled in and ampoule and the ampouleswere heat-sealed.

PREPARATION 10 Hard Capsules

α-Tocopheryl geranylacetate (25 g) and 7.5 g of polyoxyethylene-castoroil were dissolved in acetone and then 25 g of anhydrous silicic acidwas mixed in. After evaporating the acetone off, the resulting productwas mixed with 5 g of carboxymethylcellulose calcium, 5 g of cornstarch, 7.5 g of hydroxypropylcellulose and 20 g of microcrystallinecellulose, and the whole was kneaded with the addition of 30 ml ofwater. The product was made into granules through a pelletizer equippedwith a No. 24 mesh screen (B.S.) ("Xtruder Twin"® of Fuji-Paudal Co.).The granules were dried to reduce the water content thereof to less than5% and then sieved through a No. 16 mesh screen (B.S.). The granuleswere then filled into capsules using a filling machine at the rate of190 mg per capsule.

PREPARATION 11 Soft Capsules

α-Tocopheryl decaprenyl acetate (50 g) and 130 g of fractionated coconutoil were mixed together to form homogeneous solution. A gelatin solutionconsisting of 93 g of gelatin, 19 g of glycerol, 10 g of D-sorbitol, 0.4g of ethyl p-hydroxybenzoate, 0.2 g of propyl p-hydroxybenzoate and 0.4g of titanium dioxide was prepared. Using this gelatin solution inmanual punching method, soft capsules each containing 180 mg wereprepared.

PREPARATION 12 Solution for Injection

α-Tocopheryl phytylacetate (5 g), a proper quantity of arachis oil and 1g of benzyl alcohol were mixed together and the whole quantity was madeto 100 ml with the addition of additional arachis oil. One ml each ofthe solution was aseptically filled in an ampoule and the ampoules wereheat sealed.

PREPARATION 13 Hard Capsules

Decaprenol (25 g) and 7.5 g of polyoxy ethylene-castor oil weredissolved in acetone and then 25 g of anhydrous silicic acid was added.After evaporating the acetone off, the resulting product was mixed with5 g of carboxymethylcellulose calcium, 5 g of corn starch, 7.5 g ofhydroxypropylcellulose and 20 g of microcrystalline cellulose, and thewhole was kneaded with the addition of 30 ml of water. The product wasmade into granules through a pelletizer equipped with a No. 24 meshscreen (B.S.) ("Xtruder Twin"® of Fuji-Paudal Co.). The granules weredried to reduce the water content thereof to less than 5% and thensieved through a No. 16 mesh screen (B.S.). The granules were thenfilled into capsules using a filling machine at the rate of 190 mg percapsule.

PREPARATION 14 Soft Capsules

Solanesol (50 g) and 130 g of fractionated coconut oil were mixedtogether to form a homogeneous solution. A gelatin solution consistingof 93 g of gelatin, 19 g of glycerol, 10 g of D-sorbitol, 0.4 g of ethylp-hydroxybenzoate, 0.2 g of propyl p-hydroxybenzoate and 0.4 of titaniumdioxide was prepared. Using this gelatin solution in manual punchingmethod, soft capsules each containing 180 mg of content were prepared.

PREPARATION 15 Solution for Injection

Saturated decaprenol (5 g), a proper quantity of arachis oil and 1 g ofbenzyl alcohol were mixed together and the whole quantity was made to100 ml with the addition of additional arachis oil. One milliliter eachof the solution was aseptically filled in an ampoule and the ampouleswere heat sealed.

What we claim is:
 1. An antiulcer composition which comprises, as activeingredient, an antiulcer effective amount of a compound selected fromthe group consisting of phytyl oleate and isophytyl oleate in apharmaceutically acceptable carrier.